CMV boosts immune response in the young

Cytomegalovirus (CMV) has long been thought of as a sleeper agent—present in a latent form in most people but dangerous when activated in immunosuppressed individuals. Now, Furman et al. look more closely at the effects of CMV infection in young, healthy people. They find that in contrast to aged individuals where CMV infection decreased response to flu vaccine, CMV infection actually enhanced the response to flu vaccine in young adults. This beneficial effect was also seen in mice. These data suggest that latent CMV infection may be beneficial to the host, and provide a possible explanation for the prevalence of CMV infection worldwide.

Abstract

Cytomegalovirus (CMV) is a β-herpesvirus present in a latent form in most people worldwide. In immunosuppressed individuals, CMV can reactivate and cause serious clinical complications, but the effect of the latent state on healthy people remains elusive. We undertook a systems approach to understand the differences between seropositive and negative subjects and measured hundreds of immune system components from blood samples including cytokines and chemokines, immune cell phenotyping, gene expression, ex vivo cell responses to cytokine stimuli, and the antibody response to seasonal influenza vaccination. As expected, we found decreased responses to vaccination and an overall down-regulation of immune components in aged individuals regardless of CMV status. In contrast, CMV-seropositive young adults exhibited enhanced antibody responses to influenza vaccination, increased CD8+ T cell sensitivity, and elevated levels of circulating interferon-γ compared to seronegative individuals. Experiments with young mice infected with murine CMV also showed significant protection from an influenza virus challenge compared with uninfected animals, although this effect declined with time. These data show that CMV and its murine equivalent can have a beneficial effect on the immune response of young, healthy individuals, which may explain the ubiquity of CMV infection in humans and many other species.